The biocompatability of bioactive glasses, as evidenced by tight apposition of hard tissue to implanted glassy particles, has been demonstrated continuously since 1971. Specifically, the composition of one such bioactive glass, 45S5 Bioglass.RTM., was originally reported by Hench et al., J. Biomed. Mater. Res. Symp., 2: 117-141 (1971). The nature of the bone tissue/glass interface has been discussed in terms of the formation of a reactive region on the surface of the glass. It has been established that ionic exchange between the extracellular fluid and the glass at the surface transforms the silica constituent of the glass to a gel while increasing the pH of the surrounding local environment. Simultaneously, a thin layer of calcium phosphate forms on the outer surface of the glass mediated through cellular activity. Bone grows by apposition onto bioactive glass placed adjacent to bony surfaces and new bone may be conducted subsequently, over short distances. In the instance in which the bioactive glass is in the form of granules, new bone can be conducted from granule to granule.
Granules of bioactive glass have been described previously. U.S. Pat. No. 4,239,113 describes a composition for the preparation of bone cement. The cement has an inorganic portion which comprises between 15 and 75% by weight of the cement. The inorganic portion further contains bio-active glass ceramic powder having a particle size of 10-200 micrometers in a portion of 90-99% by weight and between 1-10% vitreous mineral fibers by weight. The bone cement composition further contains an admixture of methylmethacrylate copolymers and methylmethacrylate, a curing catalyst, and, preferably, an accelator.
U.S. Pat. No. 4,851,046 describes compositions containing particles of 45S5 Bioglass.RTM. of various size ranges for use in periodontal applications. It was asserted that particles of a larger size range might produce a more clinically desirable mixture. A particle size range of 90-710 micrometers was specifically described as being the most effective. The glass powders mixed well with blood and formed a cohesive mix, which also stopped the bleeding.
U.S. Pat. No. 5,204,106, issued to Schepers, et al. on Apr. 20, 1993 (incorporated herein by reference), discloses that particles of bioactive glass having the composition of 45S5 within the narrow size range of 280 to 425 micrometers (.mu.m) elicit a distinctively altered biologic response from that described previously. Particles within this specific size range were implanted into the jaw bone of young adult dogs and became disintegrated from the inside, i.e. excavated, disappeared, and were progressively and rapidly replaced by osseous tissue rather than by fibrous tissue. It is disclosed that, as the particles disintegrate, the interior constitutes a highly protected medium, which makes it possible to create and maintain conditions favorable to the differentiation of mesenchymal cells into osteoblasts. When 45S5 bioactive glass particles outside the specified size range were implanted, however, excavation was not observed. With larger particles (i.e., 425-850 .mu.m), there was no central disintegration with glass resorption or dissolving and substitution by osseous tissue. External growth of osseous tissue by osteoconduction from the cavity wall was observed, but the particles in the center of the cavity were surrounded by fibrous tissue. With smaller particles (i.e. 212-300 .mu.m), osteoconduction was observed from the cavity wall, but, again, the particles in the center were surrounded by fibrous tissue, prior to disappearing under the action of phagocytic cells.
The particles disclosed in Schepers et al. have also been used in orthopaedic sites with success. Specifically, particles in the range of 300 to 355 .mu.m have been implanted into the ankle of a patient to fill screw holes upon removal of a bone plate. X-ray follow-up revealed that the granules stimulated bone tissue formation.
Notably, the bone formation observed in Schepers et al. occurs throughout the entire defect through osteogenesis by osteostimulation, assisted by osteoconduction due to the calcium phosphate layer which is formed prior to the central, cellularly mediated disintegration. Upon central disintegration, the bioactive glass particles are fully transformed into calcium phosphate. The composition and size of the preferred granules in the Schepers et al. patent are such that the particles are gradually transformed as the defect site becomes vascularized and populated with bone tissueforming cells. The smaller particles reacted too rapidly, generating an acute inflammatory response, and thereby impeding bone tissue formation.
The material described in the Schepers et al. patent is suitable for many instances of defect repair where particles of increased bone tissue forming capability are not necessary. However, there remains a need for a material with greater reactivity in some applications of defect repair. Those instances are described in more detail below.